Combined Assessment of FFR and CFR for Decision Making in Coronary Revascularization: From the Multicenter International ILIAS Registry

ObjectivesThe aim of this study was to demonstrate the clinical implications of combined assessment of fractional flow reserve (FFR) and coronary flow reserve (CFR).BackgroundCombined assessment of FFR and CFR allows detailed characterization of pathophysiology in chronic coronary syndromes. Data on the clinical implications of distinct FFR and CFR patterns are limited, leading to uncertainty regarding their relevance.MethodsPatients with chronic coronary syndromes and obstructive coronary artery disease were selected from the multicenter ILIAS (Inclusive Invasive Physiological Assessment in Angina Syndromes) registry. Patients were classified into 4 groups on the basis of FFR ≤0.80 and CFR <2.0. The endpoint was the 5-year target vessel failure (TVF) rate.ResultsA total of 2,143 patients with 2,725 lesions were included. Compared with normal FFR/normal CFR, low FFR/low CFR carried the highest risk for TVF (HR: 5.4; 95% CI: 3.2-9.3; P < 0.001), significantly higher than in revascularized vessels (P = 0.007). Discordance, with either low FFR/normal CFR or normal FFR/low CFR, was associated with increased TVF rates compared with normal FFR/normal CFR (low FFR/normal CFR: HR: 3.5 [95% CI: 2.2-5.4; P < 0.001]; normal FFR/low CFR: HR: 3.0 [95% CI: 1.9-4.7; P < 0.001]). No difference in 5-year TVF was observed between the 2 discordant groups (P = 0.57) or between the discordant groups and the revascularized group (P = 0.26 vs low FFR/normal CFR; P = 0.60 vs normal FFR/low CFR).ConclusionsImpaired coronary hemodynamics are uniformly associated with increased 5-year TVF rates. Nonrevascularized vessels with discordant FFR and CFR are associated with 5-year event rates that are equivalent to those of vessels that undergo revascularization, whereas vessels with combined low FFR and CFR exhibit event rates that are significantly higher than after revascularization. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234)     

Differential Prognostic Value of Revascularization for Coronary Stenosis With Intermediate FFR by Coronary Flow Reserve

ObjectivesThe authors sought to evaluate comparative prognosis between deferred versus performed percutaneous coronary intervention (PCI) according to coronary flow reserve (CFR) values of patients with intermediate fractional flow reserve (FFR).BackgroundFor coronary stenosis with intermediate FFR, the prognostic value of PCI remains controversial. The prognostic impact of PCI may be different according to CFR in patients with intermediate FFR.MethodsFrom the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry, N = 2,322), 400 patients (412 vessels) with intermediate FFR (0.75-0.80) were selected. Patients were stratified into preserved CFR (>2.0, n = 253) and depressed CFR (≤2.0, n = 147) cohorts. Per-vessel clinical outcomes during 5 years of follow-up were compared between deferred versus performed PCI groups in both cohorts. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization.ResultsAmong the study population, PCI was deferred for 210 patients (219 vessels, 53.2%) (deferred group) and performed for 190 patients (193 vessels, 46.8%) (performed group). The risk of TVF was comparable between the deferred and performed groups (12.8% vs 14.2%; adjusted HR: 1.403; 95% CI: 0.584-3.369; P = 0.448). When stratified by CFR, PCI was performed in 39.1% (100/261 vessels) of the preserved CFR cohort and 61.9% (93/151 vessels) of the depressed CFR cohort. Within the preserved CFR cohort, the risk of TVF did not differ significantly between the deferred and performed groups (11.0% vs 13.9%; adjusted HR: 0.770; 95% CI: 0.262-2.266; P = 0.635). However, in the depressed CFR cohort, the deferred group had a significantly higher risk of TVF than the performed group (17.2% vs 14.2%; adjusted HR: 4.932; 95% CI: 1.312-18.53; P = 0.018). A significant interaction was observed between CFR and the treatment decision (interaction P = 0.049). Results were consistent after inverse probability weighting adjustment.ConclusionsIn patients with intermediate FFR of 0.75 to 0.80, the prognostic value of PCI differed according to CFR, with a significant interaction. PCI was associated with a lower risk of TVF compared with the deferral strategy when CFR was depressed (≤2.0), but there was no difference when CFR was preserved (>2.0). CFR could be used as an additional risk stratification tool to determine treatment strategies in patients with intermediate FFR. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234)     

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome

BackgroundOptical coherence tomography–derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain.ObjectivesThis study sought to investigate the relationship between post–percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS).MethodsThis retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI.ResultsAmong 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF.ConclusionsVessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858)     

Influence of Anatomical and Clinical Characteristics on Long-Term Prognosis of FFR-Guided Deferred Coronary Lesions

ObjectivesThe aim of this study was to evaluate the clinical and anatomical features to predict the long-term outcomes in patients with fractional flow reserve (FFR)–guided deferred lesions, verified by intravascular ultrasound (IVUS).BackgroundDeferral of nonsignificant lesion by FFR is associated with a low risk of clinical events. However, the impact of combined information on clinical and anatomical factors is not well known.MethodsThe study included 459 patients with 552 intermediate lesions who had deferred revascularization on the basis of a nonischemic FFR (>0.80). Grayscale IVUS was examined simultaneously. The primary endpoint was patient-oriented composite outcome (POCO) (a composite of all-cause death, myocardial infarction, and any revascularization) during 5-year follow-up.ResultsThe rate of 5-year POCO was 9.8%. Diabetes mellitus (hazard ratio: 3.50; 95% confidence interval [CI]: 1.86 to 6.57; p < 0.001), left ventricular ejection fraction ≤40% (hazard ratio: 4.80; 95% CI: 1.57 to 14.63; p = 0.006), and positive remodeling (hazard ratio: 2.04; 95% CI: 1.03 to 4.03; p = 0.041) were independent predictors for POCO. When the lesions were classified according to the presence of the adverse clinical characteristics (diabetes, left ventricular ejection fraction ≤40%) or adverse plaque characteristics (positive remodeling, plaque burden ≥70%), the risk of POCO was incrementally increased (4.3%, 13.6%, and 21.3%, respectively; p < 0.001).ConclusionsIn patients with FFR-guided deferred lesions, 5-year clinical outcomes were excellent. Lesion-related anatomical factors from intravascular imaging as well as patient-related clinical factors could provide incremental information about future clinical risks.     

Clinical and Prognostic Impact From Objective Analysis of Post-Angioplasty Fractional Flow Reserve Pullback

ObjectivesThis study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI).BackgroundRecent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings.MethodsA total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient.ResultsAmong the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators’ assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen’s kappa = 0.633 to 0.819; P < 0.001; intraclass correlation coefficient: 0.776 to 0.901; P < 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P < 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012).ConclusionsObjective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560)     

Trans-Stent FFR Gradient as a Modifiable Integrant in Predicting Long-Term Target Vessel Failure

BackgroundFractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with long-term outcomes. Data relating FFR-based trans-stent gradient (TSG) after PCI to long-term outcomes are sparse.ObjectivesThe aim of this study was to test whether TSG is associated with adverse events at follow-up after PCI.MethodsData were gathered from a prospective registry evaluating 501 vessels in 416 patients with median follow-up period of 596 days. Primary endpoints were: 1) target vessel failure (TVF), including target vessel revascularization, and target vessel myocardial infarction after discharge; and 2) major adverse cardiac events (MACE) including TVF, target vessel revascularization, nontarget vessel MI, cardiac death.ResultsAfter PCI, median post-PCI FFR was 0.86 and median TSG was 0.04. TSG >0.04 was associated with increased rates of TVF (8.7% vs 2.9%; P = 0.014) and MACE (17.8% vs 9.2%; P = 0.02). Post-PCI FFR < 0.86 was associated with increased rates of TVF (6.1% vs 2.2%; P = 0.03) and MACE (16.5% vs 10%; P = 0.036). The vessel subgroup with high TSG and low FFR had significantly higher rates of TVF (10.2%; P = 0.02) and MACE (20.1%; P = 0.049) than vessels with: 1) high TSG and high FFR (TVF, 2.9%; MACE, 9.7%); 2) low TSG and low FFR (TVF, 3.8%; MACE, 11.3%); and 3) low TSG high FFR (TVF, 2.2%; MACE, 7.5%). In multivariate analysis, TSG was independently predictive of TVF.ConclusionsHigher TSG was an independent predictor of adverse events, particularly TVF, and identified a subgroup of patients at higher risk for poor outcomes. The combination of high TSG and low FFR showed significantly worse outcomes compared with an “ideal result” (high FFR and low TSG). These data support a recommendation to use TSG during FFR evaluation to determine the functional success of PCI.     

Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization

ObjectivesThis study sought to evaluate the ability of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to reduce the risk of complex coronary atherosclerosis requiring revascularization.BackgroundPCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.MethodsFOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was a randomized trial of the PCSK9 inhibitor evolocumab versus placebo in 27,564 patients with stable atherosclerotic cardiovascular disease on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG).ResultsIn this study, 1,724 patients underwent coronary revascularization, including 1,482 who underwent PCI, 296 who underwent CABG, and 54 who underwent both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (hazard ratio [HR]: 0.78; 95% CI: 0.71 to 0.86; p < 0.001), simple PCI by 22% (HR: 0.78; 95% CI: 0.70 to 0.88; p < 0.001), complex PCI by 33% (HR: 0.67; 95% CI: 0.54 to 0.84; p < 0.001), CABG by 24% (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.019), and complex revascularization by 29% (HR: 0.71; 95% CI: 0.61 to 0.84; p < 0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in the first, second, and beyond second years).ConclusionsAdding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER); NCT01764633.)     

Platelet Reactivity and Clinical Outcomes After Drug-Eluting Stent Implantation: Results From the PTRG-DES Consortium

BackgroundThe long-term prognostic implication of platelet reactivity after percutaneous coronary intervention (PCI) is not clearly known.ObjectivesThe impacts of platelet reactivity from the PTRG-DES consortium were assessed.MethodsThe primary endpoint was the major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, stent thrombosis, or stroke. Key secondary endpoints were all-cause mortality, major bleeding, and net adverse clinical events (NACE), including MACCE and bleeding.ResultsBetween 2003 and 2018, a total of 11,714 patients were enrolled and grouped into tertiles according to P2Y₁₂ reaction units (PRUs): high PRUs (≥253), intermediate PRUs (188-252), and low PRUs (<188). The Kaplan-Meier (KM) estimates of the primary outcome were significantly different across the groups; the high-PRU group showed the highest MACCE rate at 5 years (12.9%, 11.1%, and 7.0% in high-, intermediate-, and low-PRU groups, respectively; P < 0.001), as well as at 1 year (P < 0.001). The high-PRU group had the greatest KM estimates of all-cause death (8.2%, 5.9%, and 3.7%, respectively; P < 0.001) at 5 years without significant differences of major bleeding, and resultant of a higher KM estimates of NACE (15.7%, 13.6%, and 9.7%, respectively; P < 0.001). A PRU ≥252, the best cutoff value, was strongly related to MACCE (HR: 1.39; 95% CI: 1.11-1.74; P = 0.003) and all-cause death at 5 years after PCI (HR: 1.42; 95% CI: 1.04-1.94; P = 0.026). The optimal cutoff value of aspirin reaction units predicting the MACCE occurrence was ≥414 and was significantly associated with 5-year MACCE occurrence or all-cause death (P < 0.001).ConclusionsIn this large-scale cohort, high PRU was significantly associated with occurrence of MACCE, all-death death, and NACE at 5 years, as well as 1 year after PCI. (PTRG-DES Consortium [PTRG]; NCT04734028)     

Role of Post-Stent Physiological Assessment in a Risk Prediction Model After Coronary Stent Implantation

ObjectivesThe aim of this study was to develop a risk model incorporating clinical, angiographic, and physiological parameters to predict future clinical events after drug-eluting stent implantation.BackgroundPrognostic factors after coronary stenting have not been comprehensively investigated.MethodsA risk model to predict target vessel failure (TVF) at 2 years was developed from 2,200 patients who underwent second-generation drug-eluting stent implantation and post-stent fractional flow reserve (FFR) measurement. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. A random survival forest model with automatic feature selection by minimal depth analysis was used for risk model development.ResultsDuring 2 years of follow-up, the cumulative incidence of TVF was 5.9%. From clinical, angiographic, and physiological parameters, 6 variables were selected for the risk model in order of importance within the model as follows: total stent length, post-stent FFR, age, post-stent percentage diameter stenosis, reference vessel diameter, and diabetes mellitus. Harrell’s C index of the random survival forest model was 0.72 (95% confidence interval [CI]: 0.62 to 0.82). This risk model showed better prediction ability than models with clinical risk factors alone (Harrell’s C index = 0.55; 95% CI: 0.41 to 0.59; p for comparison = 0.005) and with clinical risk factors and angiographic parameters (Harrell’s C index = 0.65; 95% CI: 0.52 to 0.77; p for comparison = 0.045). When the patients were divided into 2 groups according to the median of total stent length (30 mm), post-stent FFR and total stent length showed the highest variable importance in the short- and long-stent groups, respectively.ConclusionsA risk model incorporating clinical, angiographic, and physiological predictors can help predict the risk for TVF at 2 years after coronary stenting. Total stent length and post-stent FFR were the most important predictors. (International Post PCI FFR Registry; NCT04012281)     

FFR-Guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care: The FFR REACT Trial

BackgroundPost–percutaneous coronary intervention (PCI) fractional flow reserve (FFR) <0.90 is common and has been related to impaired patient outcome.ObjectivesThe authors sought to evaluate if PCI optimization directed by intravascular ultrasound (IVUS) in patients with post-PCI FFR <0.90 could improve 1-year target vessel failure (TVF) rates.MethodsIn this single-center, randomized, double-blind trial, patients with a post-PCI FFR <0.90 at the time of angiographically successful PCI were randomized to IVUS-guided optimization or the standard of care (control arm). The primary endpoint was TVF (a composite of cardiac death, spontaneous target vessel myocardial infarction, and clinically driven target vessel revascularization) at 1 year.ResultsA total of 291 patients with post-PCI FFR <0.90 were randomized (IVUS-guided optimization arm: n = 145/152 vessels, control arm: n = 146/157 vessels). The mean post-PCI FFR was 0.84 ± 0.05. A total of 104 (68.4%) vessels in the IVUS-guided optimization arm underwent additional optimization including additional stenting (34.9%) or postdilatation only (33.6%), resulting in a mean increase in post-PCI FFR in these vessels from 0.82 ± 0.06 to 0.85 ± 0.05 (P < 0.001) and a post-PCI FFR ≥0.90 in 20% of the vessels. The 1-year TVF rate was comparable between the 2 study arms (IVUS-guided optimization arm: 4.2%, control arm: 4.8%; P = 0.79). There was a trend toward a lower incidence of clinically driven target vessel revascularization in the IVUS-guided optimization arm (0.7% vs. 4.2%, P = 0.06).ConclusionsIVUS-guided post-PCI FFR optimization significantly improved post-PCI FFR. Because of lower-than-expected event rates, post-PCI FFR optimization did not significantly lower TVF at the 1-year follow-up.     

Invasive Approaches in the Management of Cocaine-Associated Non–ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to determine the impact of invasive approaches and revascularization in patients with cocaine-associated non–ST-segment elevation myocardial infarction (NSTEMI).BackgroundThe role of invasive approaches in cocaine-associated NSTEMI is uncertain.MethodsThis retrospective cohort study identified 3,735 patients with NSTEMI and history of cocaine use from the Nationwide Readmissions Database from 2016 to 2017. Invasive approaches were defined as coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Revascularization was defined as PCI and CABG. The primary efficacy outcome was major adverse cardiac events (MACE), and the primary safety outcome was emergent revascularization. Nonadherence was identified using appropriate International Classification of Diseases-Tenth Revision codes. Two propensity-matched cohorts were generated (noninvasive vs. invasive and noninvasive vs. revascularization) through multivariate logistic regression.ResultsIn the propensity score–matched cohorts, an invasive approach (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.56 to 0.92; p = 0.008) and revascularization (HR: 0.54; 95% CI: 0.40 to 0.73; p < 0.001) (compared with a noninvasive approach) were associated with a lower rate of MACE, without an increase in emergent revascularization. On stratification, PCI and CABG individually were associated with a lower rate of MACE. Emergent revascularization was increased with PCI (HR: 1.78; 95% CI: 1.12 to 2.81; p = 0.014) but not with CABG. Nonadherent patients after PCI and CABG did not have significant difference in rate of MACE. PCI in nonadherent patients was associated with an increase in emergent revascularization (HR: 4.45; 95% CI: 2.07 to 9.57; p < 0.001).ConclusionsInvasive approaches and revascularization for cocaine-associated NSTEMI are associated with lower morbidity. A history of medical nonadherence was not associated with a difference in morbidity but was associated with an increased risk for emergent revascularization with PCI.     

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Complex Coronary Artery Disease

ObjectivesThe aim of this study was to compare, in a cohort of patients with complex coronary artery disease (CAD) and severe aortic stenosis (AS), the clinical outcomes associated with transfemoral transcatheter aortic valve replacement (TAVR) (plus percutaneous coronary intervention [PCI]) versus surgical aortic valve replacement (SAVR) (plus coronary artery bypass grafting [CABG]).BackgroundPatients with complex CAD were excluded from the main randomized trials comparing TAVR with SAVR, and no data exist comparing TAVR + PCI vs SAVR + CABG in such patients.MethodsA multicenter study was conducted including consecutive patients with severe AS and complex CAD (SYNTAX [Synergy Between PCI with Taxus and Cardiac Surgery] score >22 or unprotected left main disease). A 1:1 propensity-matched analysis was performed to account for unbalanced covariates. The rates of major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, nonprocedural myocardial infarction, need for new coronary revascularization, and stroke, were evaluated.ResultsA total of 800 patients (598 undergoing SAVR + CABG and 202 undergoing transfemoral TAVR + PCI) were included, and after propensity matching, a total of 156 pairs of patients were generated. After a median follow-up period of 3 years (interquartile range: 1-6 years), there were no significant differences between groups for MACCE (HR for transfemoral TAVR vs SAVR: 1.33; 95% CI: 0.89-1.98), all-cause mortality (HR: 1.25; 95% CI: 0.81-1.94), myocardial infarction (HR: 1.16; 95% CI: 0.41-3.27), and stroke (HR: 0.42; 95% CI: 0.13-1.32), but there was a higher rate of new coronary revascularization in the TAVR + PCI group (HR: 5.38; 95% CI: 1.73-16.7).ConclusionsIn patients with severe AS and complex CAD, TAVR + PCI and SAVR + CABG were associated with similar rates of MACCE after a median follow-up period of 3 years, but TAVR + PCI recipients exhibited a higher risk for repeat coronary revascularization. Future trials are warranted.     

Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention

BackgroundPotent P2Y₁₂ agents such as ticagrelor and prasugrel are increasingly utilized across the clinical spectrum of patients undergoing percutaneous coronary intervention (PCI). There is a paucity of data supporting their use in a patient population inclusive of both acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients.ObjectivesThe authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort.MethodsConsecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year.ResultsOverall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis.ConclusionsIn this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.     

Prognostic Value of Stress Cardiac Magnetic Resonance in Patients With Known Coronary Artery Disease

ObjectivesThis study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States.BackgroundDespite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing.MethodsFrom the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined.ResultsOut of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P < 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P < 0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P < 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively.ConclusionsIn a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a <2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891)     

Short-Term Risk Stratification of Non–Flow-Limiting Coronary Stenosis by Angiographically Derived Radial Wall Strain

BackgroundDeferred revascularization of mildly stenotic coronary vessels based exclusively on physiological evaluation is associated with up to 5% residual incidence of future adverse events at 1 year.ObjectivesWe aimed to evaluate the incremental value of angiography-derived radial wall strain (RWS) in risk stratification of non–flow-limiting mild coronary narrowings.MethodsThis is a post hoc analysis of 824 non–flow-limiting vessels in 751 patients from the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) trial. Each individual vessel had ≥1 mildly stenotic lesion. The primary outcome was vessel-oriented composite endpoint (VOCE), defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction (nonprocedural), and ischemia-driven target vessel revascularization at 1-year follow-up.ResultsDuring 1-year follow-up, VOCE occurred in 46 of 824 vessels, with a cumulative incidence of 5.6%. Maximum RWS (RWS_max) was predictive of 1-year VOCE with an area under the curve of 0.68 (95% CI: 0.58-0.77; P < 0.001). The incidence of VOCE was 14.3% in vessels with RWS_max >12% vs 2.9% in those with RWS_max ≤12%. In the multivariable Cox regression model, RWS_max >12% was a strong independent predictor of 1-year VOCE in deferred non–flow-limiting vessels (adjusted HR: 4.44; 95% CI: 2.43-8.14; P < 0.001). The risk of deferred revascularization based on combined normal RWS_max and Murray–law-based quantitative flow ratio (μQFR) was significantly reduced compared with μQFR alone (adjusted HR: 0.52; 95% CI: 0.30-0.90; P = 0.019).ConclusionsAmong vessels with preserved coronary flow, angiography-derived RWS analysis has the potential to further discriminate vessels at risk of 1-year VOCE. (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease [FAVOR III China Study]; NCT03656848)     

Distal vs Conventional Radial Access for Coronary Angiography and/or Intervention: A Meta-Analysis of Randomized Trials

BackgroundEmerging evidence from randomized clinical trials (RCTs) comparing distal radial access (DRA) with conventional radial access (RA) is available.ObjectivesThe aim of this study was to provide a quantitative appraisal of the effects of DRA) vs conventional RA for coronary angiography with or without intervention.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for RCT comparing DRA vs conventional RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up.ResultsFourteen studies enrolling 6,208 participants were included. Compared with conventional RA, DRA was associated with a significant lower risk of RAO, either detected at latest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23-0.56; P < 0.001; number needed to treat [NNT] = 30) or in-hospital (RR: 0.32; 95% CI: 0.19-0.53; P < 0.001; NNT = 28), as well as EASY (Early Discharge After Transradial Stenting of Coronary Arteries) ≥II hematoma (RR: 0.51; 95% CI: 0.27-0.96; P = 0.04; NNT = 107). By contrast, DRA was associated with a higher risk of access site crossover (RR: 3.08; 95% CI: 1.88-5.06; P < 0.001; NNT = 12), a longer time for radial puncture (standardized mean difference [SMD]: 3.56; 95% CI: 0.96-6.16; P < 0.001), a longer time for sheath insertion (SMD: 0.37; 95% CI: 0.16-0.58; P < 0.001), and a higher number of puncture attempts (SMD: 0.59, 95% CI: 0.48-0.69; P < 0.001).ConclusionsCompared with conventional RA, DRA is associated with lower risks of RAO and EASY ≥II hematoma but requires longer time for radial artery cannulation and sheath insertion, more puncture attempts, and a higher access site crossover.     

Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance

BackgroundIntracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris.ObjectivesThe purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI.MethodsData was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching.ResultsIn total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697).ConclusionsIn this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris.     

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement: Meta-Analysis of Kaplan-Meier–Derived Individual Patient Data

BackgroundIt remains controversial whether prosthesis-patient mismatch (PPM) (in general considered moderate if indexed effective orifice area is 0.65-0.85 cm²/m² and severe when <0.65 cm²/m²) affects the outcomes after transcatheter aortic valve replacement (TAVR).ObjectivesThe purpose of this study is to evaluate the time-varying effects and association of PPM with the risk of overall mortality.MethodsStudy-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of studies published by December 30, 2021.ResultsIn total, 23 studies met our eligibility criteria and included a total of 81,969 patients included in the Kaplan-Meier curves (19,612 with PPM and 62,357 without PPM). Patients with moderate/severe PPM had a significantly higher risk of mortality compared with those without PPM (HR: 1.09 [95% CI: 1.04-1.14]; P < 0.001). In the first 30 months after the procedure, mortality rates were significantly higher in the moderate/severe PPM group (HR: 1.1 [95% CI: 1.05-1.16]; P < 0.001). In contrast, the landmark analysis beyond 30 months yielded a reversal of the HR (0.83 [95% CI: 0.68-1.01]; P = 0.064), but without statistical significance. In the sensitivity analysis, although the authors observed that severe PPM showed higher risk of mortality in comparison with no PPM (HR: 1.25 [95% CI: 1.16-1.36]; P < 0.001), they did not observe a statistically significant difference for mortality between moderate PPM and no PPM (HR: 1.03 [95% CI: 0.96-1.10]; P = 0.398).ConclusionsSevere PPM, but not moderate PPM, was associated with higher risk of mortality following TAVR. These results provide support to implementation of preventive strategies to avoid severe PPM following TAVR.     

10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization in Patients With Heavy Calcification

ObjectivesThe aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).BackgroundLimited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization.MethodsThis substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG).ResultsThe 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (P_interaction = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264).ConclusionsAt 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)     

10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease

BackgroundThe optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear.ObjectivesThe goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD).MethodsIn the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models.ResultsAmong 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; p_interaction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; p_interaction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: ?0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients.ConclusionsElderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)